Summary of Work: In humans and other eukaryotes the repair of DSBs is dependent upon proteins involved in chromatin structure, cell cycle response mechanisms and the enzymatic rejoining of broken DNA ends. Mutations within genes involved in break repair and in cell cycle responses to DNA strand breaks have been shown to be responsible for several human cancers and have also been implicated in the aging process. Our research efforts have focused on DSB repair in the genetically tractable yeast Saccharomyces cerevisiae. Many genes involved in DNA repair are conserved between humans and yeast. We have investigated several important aspects of DSB repair. These include i) analysis of the relative contributions of recombinational repair versus non- recombinational end-joining; ii) characterization of damage-responsive cell cycle checkpoints and identification of genes participating in these processes; iii) investigation of repair pathways available for DSBs which have alternative structures at the ends, i.e. blunt, complementary, modified, or damaged termini; and iv) systematic analysis of genes involved in the enzymatic repair of DNA strand breaks. Conclusions of this work include the following: all DSBs can be repaired by recombination mediated by the RAD52 group of DNA repair genes. Only DSBs with complementary ends are substrates for end-joining, which requires yKU70, yKU80 and RAD50. All forms of DSBs induce G2-phase arrest and this process is dependent upon RAD9 and RAD17. Genes involved in post- replication repair, including RAD5 and RAD6, are also required for DSB repair. All types of DSBs tested induce recombination and aneuploidy.